Disorders of mineral metabolism have been evaluated with methods extending from epidemiology to cellular and molecular biology. Two forms of familial hyperparathyroidism have been characterized in detail. Familial hypocalciuric hypercalcemia is an autosomal dominant trait associated with abnormal interactions with calcium in parathyroid and kidney. Familial multiple endocrine neoplasia type 1 (EMEN1) is an autosomal dominant trait causing hyperfunction of parathyroids, pancreatic iseit and anterior pituitary. It is associated with gradual but abnormal proliferation of the tissues affected. Genetic linkage studies in a large kindred have localized the MEN1 gene to the long arm of chromosome 11. Plasma from affected persons shows high mitogenic activity in plasma may contribute to primary hyperparathyroidism in EMEN1. Analysis of blood and parathyroid tumor DNA has revealed that EMEN1 parathyroids often show clonal loss of alleles in the region of the EMEN1 gene on chromosome 11. Thus the EMEN1 gene functions as a tumor suppressor gene, analogous to the retinoblastoma gene. Analysis of sporadic parathyroid adenomas revealed that 25% showed allelic loss in a similar region. Thus the clonal inactivation of the EMEN1 gene may also be a contributing factor in many sporadic parathyroid adenomas.